Current conceptual view of alzheimer's disease

The dementia known as Alzheimer's disease (AD) has been recognized as a clinical entity for nearly 100 years. The neurodegeneration that occurs during the course of the disease is complex, progressive, extensive and defies easy description. Over the years, many different hypotheses have been put forward to explain the underlying biology of AD. While the most widely known of these is the amyloid cascade hypothesis, other models have also received consideration. These alternative views recognize the role of tau, the failure of lysosomal function, abnormalities in autophagy, the loss of cell cycle control, the failure of calcium homeostasis, the establishment of a chronic inflammation and so forth. There are strengths and weaknesses to each of these conceptualizations of the disease, and this review attempts to summarize them. The chapter ends with a proposal that, befitting its complexity, the most productive way to view AD may be as a true composite of all of these mechanisms.